Primary Hyperparathyroidism: A Case-based Review

Surgery is curative in up to 95% of cases and has a low rate of complications.^2,24 A joint decision regarding treatment options is made among the patient, primary care clinician, and surgeon. Complications include vocal cord paralysis resulting from injury to the recurrent laryngeal nerve, bleeding or hematoma, laryngospasm, symptomatic hypocalcemia, and persistent hyperparathyroidism; seizures are very rare but can occur from transient hypocalcemia and hypomagnesemia.⁵ PTH levels drop by more than 50% intraoperatively if the procedure is successful; otherwise, exploration for another adenoma is indicated.¹⁰ Postoperative calcium and vitamin D supplementation are warranted once lab values are stable.

When surgery is contraindicated/refused

If surgery is indicated but the patient is a poor candidate or refuses surgery, management of hypercalcemia and bone loss with pharmacologic agents is warranted. The calcimimetic cinacalcet is a reasonable medical alternative that has been shown to adequately control hypercalcemia and hypophosphatemia and has proven effective in various patient subgroups.²⁵ This agent is useful in the treatment of patients who are asymptomatic and refuse surgery, patients with refractory PHPT after parathyroidectomy, and patients with contraindications to surgery.^24,25 The medication reduces calcium and modestly reduces PTH levels by binding parathyroid calcium-sensing receptors but does not improve bone density.^2,12 Cinacalcet is approved by the FDA for use in patients with moderate to severe disease when surgery is contraindicated.²⁴

Treatment options for osteoporosis, vertebral fractures, and progressive bone loss in the patient with PHPT include bisphosphonates. Raloxifene and estrogen replacements may be used in postmenopausal women. Oral bisphosphonates (alendronate or risedronate) are firstline therapies and have been shown to inhibit progression to osteoporosis in PHPT.^9,26 They prevent osteoclastic activity, reducing bone resorption and turnover. Contraindications to oral bisphosphonates include esophageal disorders, gastrointestinal intolerance, or inability to follow the dosing requirements. Intravenous zoledronic acid provides an alternative route of administration.

Alendronate has the best evidence for improving bone density and preventing progression to osteoporosis in patients with PHPT, but the medication does not affect calcium or PTH levels.^1,19 There is limited data on the effects of combining bisphosphonates with calcimimetics. Raloxifene is a selective estrogen receptor modulator that decreases bone resorption; it is approved for treating osteoporosis and may be used when a patient is not a good candidate for a bisphosphonate.²⁰ Denosumab, currently under study for the treatment of PHPT, is a human monoclonal antibody that improves bone density but does not affect serum calcium.²⁰ Nonpharmacologic therapies include alcohol moderation, decreased caffeine intake, weight-bearing exercise, smoking cessation, adequate hydration, and dietary modifications.²⁰

OUTCOME FOR THE CASE PATIENT

Although PHPT is often discovered incidentally in routine blood work with hypercalcemia, the case patient had developed osteoporosis and a grade IV tibial stress fracture before the diagnosis was made. Following parathyroidectomy, her hypertension worsened, requiring an additional antihypertensive medication. She developed recurrent disease and was referred to a tertiary care center for revision parathyroidectomy due to persistent elevated calcium levels. A 24-hour urine calcium test ruled out concurrent FHH. A full neck exploration was conducted and a 340-mg hypercellular parathyroid gland was removed from the left superior pole. She will be monitored for recurrent disease and will remain on a vitamin D3 supplement and treatment for osteoporosis.

CONCLUSION

Primary care clinicians should have a low threshold for initiating the work-up of mild hypercalcemia in an effort to prevent sequelae. Patient education is essential throughout the process. Understanding the condition and treatment options is necessary for a patient’s active participation in clinical decision making. Conservative management of an asymptomatic patient includes avoiding thiazide diuretics and lithium, staying well hydrated with water, maintaining moderate dietary calcium (1,000-1,200 mg/d) and vitamin D (400-600 IU/d) intake, regular exercise, and appropriate lab and bone density monitoring. Surgical treatment is recommended for symptomatic patients exhibiting decreased bone density, fractures, renal impairment, or nephrolithiasis. Treating bone loss with bisphosphonates and hypercalcemia with calcimimetics is useful. Postmenopausal women may benefit from estrogen therapy or selective estrogen receptor modulators. These agents improve bone density and lower calcium, but are often contraindicated or have adverse effects. Surgery is the only cure.³